The goal of this proposal is to investigate the molecular mechanisms controlling angiogenesis, which is critical for sustaining tumor growth. BMK1/ERK5 is a newer member of mammalian MAP kinase family and is activated by angiogenic growth factors. Recently, data generated from our conditional knockout mice of BMK1 revealed that BMK1 is critical for angiogenesis not only during the embryonic stage but also in adulthood, most likely through its role in endothelial cells (EC). To investigate and to define the function and molecular actions of BMK1 pathway in EC and in angiogenesis, we propose (1) to investigate the signaling pathway(s) that interacts with or is regulated by the BMK1 cascade in endothelial cells and (2) to explore the mechanism of action of the BMK1 cascade during angiogenesis. These proposed studies should provide new information on the regulatory mechanisms of neovascularization by which we hope to identify novel and important targets for a more effective and specific therapeutic intervention for human cancer through inhibiting tumor-associated angiogenesis. [unreadable] [unreadable] [unreadable]